It is known that in most medical procedures in which liquids are administered to a patient's body or are conveyed inside technical medical equipment, very low pressures are used, for example when setting up infusions or in medical procedures in which blood or other physiological liquids are circulated. Conventional dispensing systems for cosmetics or medical pressurised gas atomisers also generally operate at below 7 bar of liquid pressure, very rarely up to 20 bar. High pressure pumping systems, on the other hand, are generally known from various industrial applications but are not really suitable for use in technical medical equipment as they are often made of materials that are not compatible with the particular medical active substances or may even release substances that are toxic to the patients. Often, with technical medical components, it is essential that they are sterilizable. Because of the hygiene requirements imposed, components for medical equipment are generally designed for brief periods of use or even single use, so that in this field the demands for mass production are significantly increased. Moreover, industrial pumping systems are often of a mechanically complex nature so that it is difficult to reduce them to the size of handheld medical equipment, in particular.
In the treatment of lung diseases, in the meantime, the use of portable handheld equipment has become indispensable. Using such equipment therapies can be given daily, even at a distance from the practice of the doctor providing the treatment, and in this way a patient can always have access to an essential emergency medication for inhalation.
When a liquid medicament formulation is nebulised a precisely metered amount of active substance is intended to be converted into an aerosol for inhalation. The aerosol should have a small average particle size with a small droplet size distribution. In order to achieve this using nozzle pump arrangements without the use of propellants, pressures of 100-1200 bar are required in the associated pump chambers, with high demands on the leak-tight construction of the system.
By the term “medicament formulation” is meant, in the present invention, apart from medicaments, therapeutic agents or the like, particularly every kind of agent for inhalation or other forms of administration.
However, the invention is not restricted to medical nebulisation but may be used across different sectors for dispensing all kinds of liquids under pressure, for example when dispensing measured amounts of liquid in injectors, spray systems and other dispensing systems and in systems in which jets of liquid under high pressure are used (e.g. in cutting systems), even though the description that follows is directed primarily to medical applications and the preferred nebulisation of a medicament formulation for inhalation. Moreover, high pressure chambers of this kind and the manufacturing techniques associated with them may be used in totally different industrial fields such as the motor industry, for example, although this invention relates primarily to pumping situations in which particularly clean handling of the liquid in question is essential, as for example in medical technology in the pharmaceutical industry or food technology.
WO 91/14468 A1 and WO 97/12687 A1 describe nebulisers or miniaturised high pressure nebulisers. These comprise as the reservoir for a medicament preparation that is to be nebulised an insertable rigid container with an inner bag and a manually operated pressure generator with a drive spring for conveying and nebulising the medicament preparation. A container of this kind, as disclosed in WO 96/06011 A1 and WO 00/49988 A2, holds a volume of about 2-10 ml. An alternative nebuliser to those mentioned above has become known from the prior art in the meantime and is shown by way of example in FIG. 1 and described in detail hereinafter. In this nebuliser, a multipart pumping chamber is used. The strength-determining components of this substantially circular cylindrical pumping chamber are a guide tube for the pumping piston which is guided in a longitudinally movable manner, at the reservoir end a support ring which is fixed by a screwed-on cap-like retaining element and, at the other end of the pumping chamber, a nozzle holder fixed by a similar screwed-on cap-like retaining element. Details of possible microstructures for the expulsion nozzle held by the nozzle holder are disclosed in the specifications WO 94/07607, WO 99/16530 and WO 2005/000476 A1.
The components used for the pump chamber are subject to particular requirements regarding the strength of the material. Often, they cannot be made of the comparatively cheap plastics that are otherwise conventional for mass produced components in medical technology. The retaining elements described are typically metal components manufactured on lathes.
US 2002/0176788 shows, inter alia, a high pressure pump body the wall of which consists of thin walled tubing and in which the strength-determining components are not screwed together but joined to connecting elements by means of a crimped sealing bead. An outlet valve with sealing elements is inserted in the thin walled tubing. The tubing is pressed into a suitable recess in the valve unit so as to engage in a positively locking manner. When the high pressure envisaged is reached in the high pressure pumping body the corresponding valve opens and allows the liquid to flow continuously to the pump outlet.
The problem on which the present invention is based is to provide a high pressure chamber with an integrated outlet nozzle, particularly for medical nebuliser or injector systems, which is suitable for industrial manufacture. Systems of this kind deliver a metered amount of liquid in short pulses. The liquid is sucked in without the use of pressure and within a short time is brought to a peak pressure in the high pressure chamber at which the liquid is dispensed (preferably directly) through a nozzle. The sealing requirements for a pulsed system of this kind have not only static but also dynamic aspects compared with continuous pumping, which means that the connecting technology, particularly between the high pressure chamber and the outlet nozzle, is subject to particular demands.
By the term high pressure chamber is meant here a chamber that is substantially circular cylindrical on the inside, in which a fluid is put under pressure and expelled by the advancing of a piston or plunger.